A Study of SYH2051 Monotherapy in Advanced Solid Tumors or in Combination With Radiotherapy in Locally Advanced Head and Neck Cancer

• ClinicalTrials.gov Identifier: NCT06011291
• Recruitment Status: Recruiting
• First Posted: August 25, 2023
• Last Update Posted: October 27, 2023
• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Information provided by (Responsible Party): CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study Description

Brief Summary:

This is an open-label, multicenter, dose-escalation phase I study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy of SYH2051 in patients with advanced solid tumors or in combination with radiotherapy (RT) in patients with locally advanced head and neck cancer.

Condition or disease	Intervention/treatment	Phase
Solid Tumors; Head and Neck Cancer	Drug: SYH2051 tablets; Radiation: Intensity-Modulated Radiation Therapy (IMRT)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 73 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SYH2051 Monotherapy in Patients With Advanced Solid Tumors or in Combination With Radiotherapy in Patients With Locally Advanced Head and Neck Cancer
• Actual Study Start Date: August 15, 2023
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: August 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: SYH2051 monotherapy dose escalation in advanced solid tumors (Phase Ia)	Drug: SYH2051 tablets; Arm A: Five dose levels will be administered sequentially. Arm B and C: Concurrently administered with RT, and 2 weeks adjuvant treatment after RT.
Experimental: Arm B: SYH2051+RT dose escalation in locally advanced head and neck cancer (Phase Ib)	Drug: SYH2051 tablets; Arm A: Five dose levels will be administered sequentially. Arm B and C: Concurrently administered with RT, and 2 weeks adjuvant treatment after RT.; Radiation: Intensity-Modulated Radiation Therapy (IMRT); Radical or adjuvant radiotherapy
Experimental: Arm C: SYH2051+RT dose expansion in locally advanced head and neck cancer (Phase Ic)	Drug: SYH2051 tablets; Arm A: Five dose levels will be administered sequentially. Arm B and C: Concurrently administered with RT, and 2 weeks adjuvant treatment after RT.; Radiation: Intensity-Modulated Radiation Therapy (IMRT); Radical or adjuvant radiotherapy

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 31 days for Arm A and 11 weeks for Arm B ]
2. Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 2 years ]
3. Maximum tolerated dose (MTD)(if any) or maximum administrated dose (MAD) [ Time Frame: up to 1 year ]
4. Recommended phase 2 dose (RP2D) of SYH2051 in combination with RT [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Phase Ia: Maximum Plasma Concentration (Cmax) [ Time Frame: 1 years ]
2. Phase Ia: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: 1 years ]
3. Phase Ia: Area under the plasma concentration-time curve from time zero to time of last measurable concentration(AUC0-last) [ Time Frame: 1 years ]
4. Phase Ia: Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) [ Time Frame: 1 years ]
5. Objective response rate (ORR) [ Time Frame: 2 years ]
6. Disease Control Rate (DCR) [ Time Frame: 2 years ]
7. Duration of locoregional control (DoLC) [ Time Frame: 2 years ]
8. Phase Ib and Ic: Concentrations of SYH2051 [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Phase Ia: Patients with histologically or cytologically confirmed advanced solid tumors, for whom there is no standard therapy available, or ineffective or intolerant to standard therapy. Phase Ib/Ic: Patients with histologically or cytologically confirmed locally advanced head and neck cancer suitable for radiotherapy alone;
3. Eastern Collaborative Oncology Group (ECOG) Performance Status of 0~1;
4. Patients in medical conditions to be able to receive radiotherapy (for phase Ib/Ic);
5. Life expectancy of >3 months;
6. At least one measurable lesion (excluding patients in phase Ic combined with adjuvant radiotherapy);
7. Patients with adequate hematologic, hepatic, renal and coagulation function;
8. Patients are not pregnant or lactating and required contraception;
9. Patients who are willing to provide written informed consent form (ICF) before the beginning of the study.

Exclusion Criteria:

1. Any antineoplastic therapy such as chemotherapy, biologic therapy, endocrine therapy, or immunotherapy within 4 weeks before the first dose of the study drug (or within 5 half-lives of other unmarketed study drugs, whichever is longer), except for the following:

   1. 6 weeks for Nitrosoureas or mitomycin C;
   2. 2 weeks or five half-lives (whichever is longer) for oral fluorouracil and small molecule targeted drugs;
   3. 2 weeks for Chinese herbal medicine with antineoplastic indications;
2. Patients with previous (within 2 years before screening) or concurrent other malignancies (only for phase Ib/Ic);
3. Patients had undergone major organ surgery (excluding needle biopsies) within 4 weeks before the first dose, with obvious trauma, or require elective surgery during the study;
4. Severe, non-healing fractures within 4 weeks before the first dose of the study drug;
5. The adverse reactions of previous antineoplastic therapy have not recovered to ≤grade 1 as determined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria;
6. Patients who had received treatment with any drug that is a medium or strong inhibitor or inducer of cytochrome P450 (CYP) 3A4/5 enzyme activity within 2 weeks before screening or need to continue receiving such drugs;
7. Active brain metastases and/or carcinomatous meningitis;
8. Concurrent serious and/or uncontrolled medical conditions at screening (e.g., severe chronic obstructive pulmonary disease);
9. Patients with abnormal thyroid function were not allowed, except those with euthyroid function after drug control;
10. History of severe cardiovascular disease;
11. History of myopathy or raised creatine kinase (CK) >5 times the upper limit of normal (ULN);
12. Known hypersensitivity or intolerance to any component of the study drug or its excipients;
13. History of autoimmune disease, immunodeficiency disease, including HIV testing positive or other acquired, congenital immunodeficiency diseases, or organ transplantation;
14. Active hepatitis B virus, hepatitis C virus or active syphilis infection;
15. Active dysphagia, malabsorption or other chronic gastrointestinal diseases or conditions that may hamper compliance and/or absorption of the study drug;
16. Other ineligibilities according to the investigator.

Contacts and Locations

Contacts

Contact: Clinical Trials Information Group officer; 86-0311-69085587; ctr-contact@cspc.cn

Locations

China, Hebei

Clinical Trials Information Group; Recruiting

Shijiazhuang, Hebei, China, 050000

Contact: Clinical Trials Information Group officer 86-0311-69085587 ctr-contact@cspc.cn

Sponsors and Collaborators

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

More Information

• Responsible Party: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• ClinicalTrials.gov Identifier: NCT06011291
• Other Study ID Numbers: SYH2051-001
• First Posted: August 25, 2023
• Last Update Posted: October 27, 2023
• Last Verified: October 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Head and Neck Neoplasms; Neoplasms; Neoplasms by Site